Capsule device having variable specific gravity

ABSTRACT

An endoscopy capsule having an image collecting capacity includes a deformable member configured to inflate when exposed to body liquid. The deformable member includes an effervescent material. When the effervescent reacts with water the resulting Carbon-Dioxide gas reduces the specific gravity of the endoscopy capsule. The capsule is contained within a shell or dome when swallowed. The shell or dome is configured dissolve in either a low or high pH environment.

CROSS REFERENCE TO RELATED APPLICATIONS

The present invention is related to PCT Patent Application Series No.PCT/US13/66011 entitled “System and Method for Capsule Device withMultiple Phases of Density”, filed on Oct. 22, 2013, PCT PatentApplication Series No. PCT/US13/39317, entitled “Optical WirelessDocking System for Capsule Camera”, filed on May 2, 2013 and PCT PatentApplication Series No. PCT/US13/42490, entitled “Capsule EndoscopicDocking System”, filed on May 23, 2013. The U.S. Patent and PCT PatentApplications are hereby incorporated by reference in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to diagnostic imaging inside the humanbody. In particular, the present invention relates to a capsule devicewith a variable specific gravity for diagnostic imaging of theGastrointestinal (GI) tract.

Description of the State of the Art

Devices for imaging body cavities or passages in vivo are known in theart and include endoscopes and autonomous encapsulated cameras.Endoscopes are flexible or rigid tubes that pass into the body throughan orifice or surgical opening, typically into the esophagus via themouth or into the colon via the rectum. An image is formed at the distalend using a lens and transmitted to the proximal end, outside the body,either by a lens-relay system or by a coherent fiber-optic bundle. Aconceptually similar instrument might record an image electronically atthe distal end, for example using a CCD or CMOS array, and transfer theimage data as an electrical signal to the proximal end through a cable.Endoscopes allow a physician control over the field of view and arewell-accepted diagnostic tools. However, they do have a number oflimitations, present risks to the patient, are invasive anduncomfortable for the patient. Additionally, patient costs typicallyassociated with imaging body cavities with an endoscope prohibits theiruse as a routine health-screening tool.

Because of the difficulty traversing a convoluted passage, endoscopescannot easily reach the majority of the small intestine. Specialtechniques and precautions are needed to reach the entirety of thecolon. Endoscopic risks include the possible perforation of bodilyorgans traversed and complications arising from anesthesia. A trade-offis often made between the extent of imaging taken of body cavities andpatient pain during the procedure, health risks and/or post-proceduraldown time associated with the use of anesthesia. Also, a large number ofpatients are uncomfortable with the concept of traditional endoscopy andare therefore refusing the procedure resulting in an increased risk ofcolorectal cancer.

An alternative in vivo image sensor that addresses many of theseproblems is the capsule endoscope. A camera is housed in a swallowablecapsule, along with a radio transmitter for transmitting data, primarilycomprising images recorded by the digital camera, to a base-stationreceiver or transceiver and data recorder outside the body. The capsulemay also include a radio receiver for receiving instructions or otherdata from a base-station transmitter. Instead of radio-frequencytransmission, lower-frequency electromagnetic signals may be used. Powermay be supplied inductively from an external inductor to an internalinductor within the capsule or from a battery within the capsule.

An autonomous capsule camera system with on-board data storage wasdisclosed in the U.S. Pat. No. 7,983,458, entitled “In Vivo AutonomousCamera with On-Board Data Storage or Digital Wireless Transmission inRegulatory Approved Band,” granted on Jul. 19, 2011. This patentdescribes a capsule system using on-board storage such as semiconductornonvolatile archival memory to store captured images. After the capsulepasses from the body, it is retrieved. A capsule housing is opened andthe images stored are transferred to a computer workstation for storageand analysis. For capsule images either received through wirelesstransmission or retrieved from on-board storage, the images aredisplayed and examined by a diagnostician to identify potentialanomalies. Alternatively, the nonvolatile archival memory may be locatedseparately or remotely from the capsule and the images transmitted tothis memory over a wireless data link.

FIG. 1 illustrates an exemplary capsule sensing system with on-boardstorage. The sensing system 110 includes illuminating system 12 and acamera that includes optical system 14 and image sensor 16. Asemiconductor nonvolatile archival memory 20 may be provided to allowthe images to be stored and later retrieved at a docking station outsidethe body, after the capsule is recovered. The sensing system 110includes battery power supply 24 and an output port 26.

Sensing system 110 may be propelled through the GI tract by peristalsis.Illuminating system 12 may be implemented by LEDs. In FIG. 1, the LEDsare located adjacent to the camera's aperture, although otherconfigurations are possible. A light source may also be provided, forexample, behind the aperture. Other light sources, such as laser diodes,may also be used. Alternatively, white light sources or a combination oftwo or more narrow-wavelength-band sources may also be used. White LEDsare available that may include a blue LED or a violet LED, along withphosphorescent materials that are excited by the LED light to emit lightat longer wavelengths. The portion of capsule housing 10 that allowslight to pass through may be made from bio-compatible glass or polymer.

Optical system 14, which may include multiple refractive, diffractive,or reflective lens elements, provides an image of the lumen walls onimage sensor 16. Image sensor 16 may be provided by charged-coupleddevices (CCD) or complementary metal-oxide-semiconductor (CMOS) typedevices that convert the received light intensities into correspondingelectrical signals. Image sensor 16 may have a monochromatic response orinclude a color filter array such that a color image may be captured(e.g. using the RGB or CYM representations). The analog signals fromimage sensor 16 are preferably converted into digital form to allowprocessing in digital form. Such conversion may be accomplished using ananalog-to-digital (A/D) converter, which may be provided inside thesensor (as in the current case), or in another portion inside capsulehousing 10. The A/D unit may be provided between image sensor 16 and therest of the system. LEDs in illuminating system 12 are synchronized withthe operations of image sensor 16. Processing module 22 may be used toprovide processing required for the system such as image processing andvideo compression. The processing module may also provide needed systemcontrol such as to control the LEDs during image capture operation. Theprocessing module may also be responsible for other functions, such asmanaging image capture and coordinating image retrieval.

After traveling through the GI tract and exiting from the body, thecapsule camera is retrieved. Its images stored in an archival memory areread out through an output port. The received images are usuallytransferred to a base station for processing and for a diagnostician toexamine. The accuracy as well as efficiency of diagnostics is mostimportant. A diagnostician is expected to examine all images andcorrectly identify all anomalies.

As the capsule device travels through the gastrointestinal (GI) tract,the capsule device will encounter different environments. It isdesirable to manage the capsule device to travel at a relatively steadyspeed so that sufficient sensor data (e.g., images) is collected alongthe desired portion of the GI tract and without wasting power orexcessive data collection.

Naturally, the density of the capsule can affect its motion through abody liquid. If the capsule density is greater than the body liquid inwhich it is found, the capsule will tend to move in the direction ofgravity. If the capsule density is less than the body liquid density andin the absence of peristalsis, the capsule will tend to move againstgravity or remain at its location, since the volume of fluid displacedby the capsule weighs more than the capsule. Thus, for a capsuleintended for collecting images in the colon including the ascendingcolon it is desirable to have a density ratio (i.e., (capsuledensity)/(body liquid)) or Specific Gravity (SG)<1, but also have SG>1before the capsule reaches the large intestine, such as when the capsuleis passing through the stomach.

SUMMARY OF THE INVENTION

The present invention discloses a capsule device capable of having itsdensity change or vary as it travels through the gastrointestinal (GI)tract. The capsule device comprises a sensor system and a densitycontrol. The sensor system may include a light source, an image sensorfor capturing image frames of a scene illuminated by the light source,an archival memory, and housing. The light source and image sensor areenclosed within the housing. The archival memory may be enclosed withinthe housing, or separate from the housing. In the latter case thearchival memory may be accessed remotely by a wireless link with thecapsule device. The capsule device is intended for being swallowed by apatient.

Embodiments of the capsule device's density control include a pouchcontaining an effervescent mixture. In some embodiments there is onepouch containing an effervescent. In other embodiments there can be morethan one pouch, each containing an effervescent. The pouch is made atleast partially from a fluid-permeable membrane material. Body fluiddiffuses through the membrane to mobilize and initiate the effervescentreaction, which tests show has the effect of reducing the SG of thecapsule device from between well above and slightly below 1, for thepurpose of facilitating passage of the capsule through different regionsof the GI tract. In some embodiments the capsule SG can vary betweenabout 1.1 and 2.0 (SG>1) and equal to and less than 1, such as between1.0 and about 0.84, or between about 0.98 and 0.87 (SG≤1). Preferably apouch or deformable member, or at least a portion thereof, is made froma material or materials that prevent or minimize diffusion of theeffervescent gas. Preferably, the at least a portion of the pouch ordeformable member is made from a material or materials that arepermeable but minimally permeable to CO2 gas and water.

In respect to transit through the GI tract, there are at least twodesignated regions where the capsule SG can differ. In one embodiment,the capsule SG is greater than one for the stomach and less than one forthe ascending colon. In another embodiment the capsule SG is less thanone for the ascending colon and greater than one for the stomach anddescending colon in order to have the capsule device assume a desiredspecific gravity within the GI tract, it is helpful to have a goodunderstanding of transit times through regions of the GI tract. Thesetransit times will of course vary from person to person and depend onsuch factors as the age, gender, race, health and anatomy of thepatient. In some embodiments the capsule SG may be configured to change,i.e., increase or decrease, based on an elapsed time from when thepatient swallows the capsule to when the capsule should have reached theregion of interest, e.g., time from swallowing the capsule to when ithas passed through the pyloric valve.

Other embodiments of a capsule device with deformable member (e.g., atethered pouch containing an effervescent mixture) include a deformablemember coated with a biodegradable, bio-erodible or bioresorbablecoating to prevent body liquid from diffusing into an interior of thedeformable member for a limited period of time, e.g., prior to thecapsule device passing through the stomach. Other embodiments include acapsule device encased or encapsulated within a biodegradable shell thatencloses the entire capsule device, or a dome that only partiallyencloses the capsule device. The coating, dome or shell embodimentsprevent body liquid from coming into contact with the deformable memberuntil the coating, dome or shell has fully or partially degraded withinthe body liquid. The coating, shell or dome is configured to degradeafter the capsule device has passed through a portion of the GI tract.As such, a capsule device with a SG>1 is maintained until afteressentially all of the biodegradable coating, shell or dome has degradedor resorbed and a fluid-permeable membrane material comes into contactwith body liquid. The coating material, or material or the shell ordome, may be essentially water soluble, enzymatic or enteric material.

A sensing system of the capsule device may have electrical contactsfixedly disposed on the housing, wherein the electrical contacts arecoupled to the archival memory so that an external device is allowed toaccess image data stored in the archival memory through the electricalcontacts. The electrical contacts may include power pins to providepower to the capsule device for data retrieval of image data stored onthe archival memory. Alternatively, inductive powering can be used toprovide power to the capsule device for data retrieval of image datastored on the archival memory. In yet another embodiment, the capsuledevice further comprises an optical transmitter to transmit an opticalsignal through a clear window, wherein image data from the archivalmemory is transmitted to an external optical receiver.

According to one aspect of the invention, there is a capsule device, acapsule endoscope, a method for making such a capsule device/endoscope,a method for assembly of a capsule device/endoscope, a system or amethod for imaging of the GI Tract including but not limited to thecolon using the capsule device having one or more, or any combination ofthe following items (1) through (8):

-   -   (1) Enteric coating, dome or shell; time-controlled coating,        dome or shell; water-soluble coating, dome or shell; and/or        enzymatic coating, dome or shell.    -   (2) The Embodiment A including one or more or, or any        combination of the parameters (a) through (i) associated with        Embodiment A.    -   (3) The Embodiment B including one or more or, or any        combination of the parameters (a) through (i) associated with        Embodiment B.    -   (4) Any of the embodiments of a pouch disclosed in FIG. 7A    -   (5) Non-volatile, archival memory for storing images, located on        device or accessed remotely by the system.    -   (6) A capsule endoscope, comprising: a sensor system comprising        a light source, an image sensor for capturing image frames of a        scene illuminated by the light source, and an archival memory; a        housing adapted for being swallowed, wherein the sensor system        is enclosed in the housing; and a pouch containing an        effervescent, the pouch being attached to the housing; wherein        at least the pouch is encapsulated within a dissolvable shell,        dome or coating; and wherein the endoscope specific gravity (SG)        is greater than 1 when the pouch is not submerged in water.    -   (7) Item (6) in combination with one or more, or any combination        of the following items (6.a) through (6.$) with item (6): (6.a)        wherein at least the pouch is encapsulated within an enteric        shell, dome or coating; (6.b) wherein the enteric coating, dome        or coating is designed to a pH in the range of 5.0-7.4 so that        the coating, dome or shell is intended to dissolve in the small        intestine; (6.c) wherein the endoscope is configured such that        the specific gravity (SG) drops below 1 in about two hours after        the pouch is exposed to water; (6.d) wherein the endoscope is        configured such that the specific gravity (SG) is less than 1        for more than about six hours after the pouch is exposed to        water; (6.e) wherein the pouch comprises polyetherblockamide        copolymers, thermoplastic polyurethanes, polyamides, polyamide        block copolymers, polyamide elastomers, polyurethanes,        polyesters, polyester copolymers, polyamide copolymers,        polyurethane copolymers, polyether copolymers, polyesteramides,        polyesteramide copolymers, polyvinyl chloride, polyvinyl        chloride copolymers, polyvinylidene dichloride, polyvinylidene        dichloride copolymers, fluoropolymers, polyvinyl fluoride,        polyvinyl fluoride copolymers, polyvinylidene difluoride,        polyvinylidene difluoride copolymers, polyvinylpyrrolidone        copolymers, or polyvinylalcohol copolymers; (6.f) wherein the        pouch has a wall thickness of less than 5 mils or less than 10        mils; (6.g) wherein the pouch water uptake in 12 hours relative        to a pouch and effervescent dry weight is less than 200% or 50%;        (6.h) wherein the pouch material is selected form the set        consisting of polyetherblockamide copolymers, thermoplastic        polyurethanes, polyamides, polyamide block copolymers, polyamide        elastomers, polyurethanes, polyesters, polyester copolymers,        polyamide copolymers, polyurethane copolymers, polyether        copolymers, polyvinyl chloride, polyvinyl chloride copolymers,        polyvinylidene dichloride, polyvinylidene dichloride copolymers,        fluoropolymers, polyvinyl fluoride, polyvinyl fluoride        copolymers, polyvinylidene difluoride, or polyvinylidene        difluoride copolymers; (6.i) wherein the Young's modulus of the        pouch is: high enough to create a non-conformal pouch; or low        enough to create a slightly conformal pouch, such that the pouch        can reach a maximum size 25% above the nominal size with a        maximum of 40 mg effervescent; (6.j) wherein the endoscope pouch        is configured such that the specific gravity (SG) is more than        for more than 1.5 hours after the pouch is exposed to water;        (6.k) wherein the endoscope pouch is configured such that the        specific gravity (SG) is <1 for more than 6 hours after the        pouch is exposed to water; (6.l) wherein the endoscope pouch is        configured such that the specific gravity (SG) is <1 for more        than 4 hours after the pouch is exposed to water; (6.m) wherein        the endoscope pouch is configured such that the specific gravity        (SG) is <1 for more than 4 hours but less than 12 hours; (6.n)        wherein the effervescent is coated; (6.o) wherein the        effervescent coating is an enteric coating designed to a pH in        the range of 5.0-7.4 such that the effervescent is intended to        react with water after the endoscope has reached the small        intestine; (6.p) wherein the pouch further comprises a        desiccant; (6.q) wherein the ratio of desiccant to effervescent        is 1:10 to 2:1; (6.r) wherein the pouch has a total exterior        surface area of about 300 and 1,000 mm2 and where the active        exterior surface area is between about 50 and 1,000 mm2; and/or        (6.s) wherein between about 10 mg and 50 mg of effervescent are        contained within the pouch.    -   (8) One, two, three or more pouches attached to the capsule.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in the presentspecification are herein incorporated by reference to the same extent asif each individual publication or patent application was specificallyand individually indicated to be incorporated by reference. To theextent there are any inconsistent usages of words and/or phrases betweenan incorporated publication or patent and the present specification,these words and/or phrases will have a meaning that is consistent withthe manner in which they are used in the present specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows schematically a capsule camera system in the GI tract,where archival memory is used to store captured images to be analyzedand/or examined.

FIGS. 2A through 2D illustrate a capsule device having an attachedpouch. FIGS. 2A and 2B show the capsule device before and after placingthe device in a dissolvable shell, such as an enteric or non-entericshell. FIG. 2C illustrates the device after the shell has dissolved andthe pouch is exposed to water. FIG. 2D illustrates the state of thedevice after the pouch has accumulated water and the CO2 hassubstantially diffused out of the pouch.

FIGS. 3A through 3B illustrate another embodiment of a capsule device.The pouch of the device is enclosed or encapsulated within a dome inFIG. 3A.

FIGS. 4A-4E illustrate an assembly process for the pouch of FIG. 3A.

FIG. 5 is a graph showing changes in SG and inflation for pouches ofcapsule devices according to two embodiments of the disclosure. Shownare plots for a change in SG for a capsule device according to anEmbodiment A and an Embodiment B, respectively. The Embodiment A capsuledevice has no enteric coating, or no shell or dome made from an entericmaterial when the capsule device is swallowed. The Embodiment B capsuledevice having an enteric coating, or shell or dome made from an entericmaterial when the capsule device is swallowed. The abscissa is time (t),where t=T0 represents the time when the capsule device is swallowed orplaced or placed in body fluid. There are two ordinates in FIG. 5. Thefirst (leftmost) ordinate refers to the percentage change in inflationfor the pouch where 100% inflation means the highest amount of inflationor gas pressure achieved within the interior of the pouch. This ordinatecorresponds to the solid curve in the graphs. The adjacent ordinaterefers to the capsule device SG and corresponds to the dashed curves.Time t=T1 represents the time when the reaction between the effervescentand water starts to take place. Time t=T2 represents the time when theSG of the device has reached about 1 and is becoming buoyant. SG isabove 1 for the period t=T2−T0. The period t=T2−T1 may correspond to aperiod of between 0.05 to 3 hours. The capsule device has an SG lessthan or equal to about 1 SG for the period t=T4−T2, which may correspondto a period of between 1 to 12 hours.

FIG. 6 is a plot showing changes in pouch inflation over time among sixdifferent configurations of a pouch containing an effervescent. Theordinate refers to a normalized inflation amount where “1” means thehighest amount of inflation or volume increase for the respective pouch.

FIG. 7A summarizes results from bench tests of inflation periods forseveral different pouch configurations according to the disclosure.

FIG. 7B report statistics (mean and standard deviation) for some of thebench tests in FIG. 7A.

FIG. 7C is a table showing the percent and amount of weight increase fordifferent pouch configurations. The change in weight is measured afterthe pouch was submerged for 12 hours. The weight percentage change ismeasured with respect to the dry weight of the pouch with effervescentand desiccant inside. For three of the cases PEG was added as adesiccant, polyacrylic acid sodium salt homo- and co-polymers are alsoeffective polymer desiccants.

FIGS. 8A-8E illustrate an example of various specific gravity or densitystates for a capsule device incorporating density control.

FIGS. 9A-9B illustrate an example of various specific gravity or densitystates for a capsule device incorporating a biodegradable plug.

FIG. 10 illustrates an example of a capsule device incorporating densitycontrol according to an embodiment of the present invention, where thehousing includes a flexible section to expand or contract.

FIGS. 11A-11B illustrate an example of a capsule device incorporatingdensity control according to an embodiment of the present invention,where the housing comprises two closely coupled parts.

FIG. 12 illustrates an example of a capsule device incorporating densitycontrol according to an embodiment of the present invention, where anextendable part is attached to the sensor system.

DETAILED DESCRIPTION

It will be readily understood that the components of the presentinvention, as generally described and illustrated in the figures herein,may be arranged and designed in a wide variety of differentconfigurations. Thus, the following more detailed description of theembodiments of the systems and methods of the present invention, asrepresented in the figures, is not intended to limit the scope of theinvention, as claimed, but is merely representative of selectedembodiments of the invention.

Reference throughout this specification to “one embodiment,” “anembodiment,” or similar language means that a particular feature,structure, or characteristic described in connection with the embodimentmay be included in at least one embodiment of the present invention.Thus, appearances of the phrases “in one embodiment” or “in anembodiment” in various places throughout this specification are notnecessarily all referring to the same embodiment.

Furthermore, the described features, structures, or characteristics maybe combined in any suitable manner in one or more embodiments. Oneskilled in the relevant art will recognize, however, that the inventioncan be practiced without one or more of the specific details, or withother methods, components, etc. In other instances, well-knownstructures, or operations are not shown or described in detail to avoidobscuring aspects of the invention.

The illustrated embodiments of the invention will be best understood byreference to the drawings, wherein like parts are designated by likenumerals throughout. The following description is intended only by wayof example, and simply illustrates certain selected embodiments ofapparatus and methods that are consistent with the invention as claimedherein.

In the description like reference numbers appearing in the drawings anddescription designate corresponding or like elements among the differentviews.

For purposes of this disclosure, the following terms and definitionsapply:

The terms “about” or “approximately” mean 30%, 20%, 15%, 10%, 5%, 4%,3%, 2%, 1.5%, 1%, between 1-2%, 1-3%, 1-5%, or 0.5%-5% less or morethan, less than, or more than a stated value, a range or each endpointof a stated range, or a one-sigma, two-sigma, three-sigma variation froma stated mean or expected value (Gaussian distribution). For example, d1about d2 means d1 is 30%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0% orbetween 1-2%, 1-3%, 1-5%, or 0.5%-5% different from d2. If d1 is a meanvalue, then d2 is about d1 means d2 is within a one-sigma, two-sigma, orthree-sigma variance from d1.

It is understood that any numerical value, range, or either rangeendpoint (including, e.g., “approximately none”, “about none”, “aboutall”, etc.) preceded by the word “about,” “substantially” or“approximately” in this disclosure also describes or discloses the samenumerical value, range, or either range endpoint not preceded by theword “about,” “substantially” or “approximately.”

An “enteric” coating, or coated shell or dome, or a dome or shell madefrom an enteric material dissolves when immersed in a pH environment ofgreater than about 5, or that dissolves in the small intestine but notin the stomach.

A shell or dome not coated with an enteric coating, or a “non-enteric”coating, or a shell or dome not made from an enteric material dissolveswhen immersed in bodily fluids at physiological temperatures. A watersoluble coating or material made from gelatin or hydroxyl propyl methylcellulose (HPMC) are examples.

A “water soluble” or “time-released” coating, shell or dome is a watersoluble coating, dome or shell that dissolves in gastric juices orwater. The coating, shell or dome can be made to dissolve from betweenabout 3, 5, or 10 minutes to 4 hours from the time when it is put incontact with body fluid.

An “enzymatic” coating, shell or dome is a coating, shell or domeconstructed to dissolve when it comes in contact with enzymes in thebody.

A “time controlled” coating, shell or dome is a coating, shell or domeconstructed to dissolve within a predetermined amount of time. Atime-controlled coating may be water soluble.

“Body liquid” means a gastric liquid, liquid present in the GI tractwhen the capsule device is in transit, water or a liquid in the GI tractthat is substantially water.

“Specific Gravity” or SG means the ratio of the density of a body to thedensity of water at 37 Deg. Celsius. A body that is buoyant or floats onthe surface of water has its SG equal to about one or less than one. Abody that sinks in water has an SG greater than one.

“a deformable member” means a body including a pouch, balloon, sack, orbag made at least partially from a fluid-permeable membrane material. Ina preferred embodiment at least a portion of the deformable member ismade from a fluid-permeable membrane material that is permeable butminimally permeable to water and CO2 gas.

In preferred embodiments the deformable member includes a pouch madeentirely from a fluid-permeable membrane material that prevents orminimizes diffusion of the effervescent gas, a tether for attaching thepouch to a capsule housing, and an effervescent contained within thepouch. The pouch is sealed so that a fluid can enter its interior onlyby diffusion through the membrane. In some embodiments there can be morethan one pouch.

A “desiccant” is a solid that absorbs water and does not release a gaswhen it encounters water. A desiccant may be silica gel, sodiumchloride, CaCl2, MgSO4, Na2SO4, CaSO4, K2CO3, Na2CO3, NaHCO3, CaO, BaO,Al2O3, P2O5, polymers and super absorbing polymers such as polyethyleneglycol (PEG), polyvinylalcohol (PVA), polyvinylpyrrolidone (PVP),cellulose, alginate, polyacrylonitrile starch graft copolymers, acylicacid acrylamide copolymers, polyvinyl alcohol copolymers, polyacrylatepolyacrylamide copolymers, sodium polyacylate or polyacrylic acid sodiumsalt (works with potassium as well), polyacryl amide copolymer, ethylenemalic anhydride copolymer, crosslinked carboxymethylclulose, andcrosslinked polyethylene oxide. The polymers can be of any molecularweight from about 3,000 to 500,000 Daltons, or have any structure suchas linear, branched, star, dendritic, or a combination of thesestructures.

An “effervescent” or “gas generating material” is a bio-compatiblematerial that when placed in aqueous solution generates carbon dioxide(CO2) or another gas. A mixture of anhydrous sodium bicarbonate andanhydrous citric acid is one example of an effervescent, a mixture ofpotassium bicarbonate and anhydrous citric acid is another example, amixture of two or more bicarbonate salts and anhydrous citric acid isanother example. In another embodiment citric acid is replaced byanother anhydrous solid state acid such as ascorbic acid or succinicacid. In preferred embodiments an effervescent mixture is used.

U.S. Pat. No. 7,192,397 and U.S. Pat. No. 8,444,554 disclose a capsuledevice. If the capsule SG is about 1 the device will suspend or float inthe liquid in the gastrointestinal (GI) tract such as in the stomach orin the colon. As disclosed in U.S. Pat. No. 7,192,397 and U.S. Pat. No.8,444,554, the capsule device will be carried through the small andlarge intestine by backpressure of a flow of liquid through the bodylumen when the capsule SG is about 1. However, a capsule SG of about 1or less than 1 may float in the stomach for some time, rather thanpassing through the pyloric valve. Thus, on the one hand, it isdesirable to have the capsule SG>1 so that the capsule device will passthrough the stomach without much difficulty. On the other hand, acapsule device with SG>1 will not will easily ascend the colon, or maysit stationary in the cecum for a long period of time. Capsule devicesaccording to one aspect of the disclosure can, however, traverse theascending colon by having the capsule device SG become less than 1 bythe time the capsule device reaches the cecum.

For a capsule device with an image sensor, it is desirable to have asteady and consistent travelling velocity inside different regions ofthe GI tract, e.g. stomach, small bowel, ascending and descending colonsso that smooth and stable images and video can be obtained. Thetravelling velocity of the capsule camera depends on many factorsincluding regional gastrointestinal motility, gravitational force,buoyancy and viscous drag of the surrounding fluids. After the capsuledevice is swallowed, it is propelled into the esophagus. Peristalticwaves in the esophagus move the capsule device into the stomach. Afterthe capsule device passes the cardia and enters the stomach fluid, thebalance among gravitational force, buoyancy and drag from the gastricfluids starts to affect its travelling velocity and transit time. Travelthrough the stomach for the capsule device may be understood through themigrating myoelectric complex or cycle (MMC). The MMC can be dividedinto four phases. Phase 1 lasts between 30 and 60 minutes with rarecontractions. Phase 2 lasts between 20 and 40 minutes with intermittentcontraction. Phase 3, or housekeeping phase, lasts between 10 and 20minutes with intense and regular contractions for short period. Thehousekeeping wave sweeps all the undigested material out of the stomachto the small bowel. Phase 4 lasts between 0 and 5 minutes and occursbetween phase 3 and phase 1 of two consecutive cycles. In the smallintestine, the BER (basic electrical rhythm) is around 12 cycles/minutein the proximal jejunum and decreases to 8 cycles/minutes in the distalileum. There are three types of smooth muscle contractions: peristalticwaves, segmentation contractions and tonic contractions. Normally,peristalsis will propel the capsule device towards the large intestines.

While the large intestine is one organ, it demonstrates regionaldifferences. The right or proximal (ascending) colon serves as areservoir and the distal (transverse and descending) colon mainlyperforms as a conduit. The character of the luminal contents impacts thetransit time. Liquid passes through the ascending colon quickly, butremains within the transverse colon for a long period of time. Incontrast, a solid meal is retained by the cecum and ascending colon forlonger periods than a liquid diet. In the ascending colon, retrogrademovements are normal and occur frequently. In order for the buoyantforce to overcome the gravitational force and retropulsion, the specificgravity of the capsule device may be decreased to less than one (e.g.,about 0.94 or less) by the time the capsule device enters the largeintestine. Additionally, the capsule device may have its SG increasedback to above 1 by the time it reaches the transverse or descendingcolon to shorten the transit time to the rectum, and/or to facilitate ormore smooth and steady motion to the rectum.

In order to properly set the specific gravity of a capsule device, oneof course needs to know when the capsule device will arrive (or hasarrived) at specific regions of the GI tract. There are various knownregion detection methods in the literature. The region detection methodsinclude estimated transit time (e.g., about 1 hour in stomach and about3-4 hours in small bowel), identification of image contents based oncaptured images by the capsule device, motion detection based on thecaptured images by the capsule device, pH detection (pH value increasingprogressively from the stomach (1.5-3.5) and the small bowel (5.5-6.8)to the colon (6.4-7.0), pressure sensor (higher luminal pressure fromperistaltic motion in the colon than that in the small bowel) andcolonic microflora. The ascending colon has a larger diameter than otherregions besides the stomach. The size may be detected by the methodsdisclosed in U.S. Patent Publications, Series No. 2007/0255098,published on Nov. 1, 2007, U.S. Patent Publications, Series No.2008/0033247 published on Feb. 7, 2008 and U.S. Patent Publications,Series No. 2007/0249900, published on Oct. 25, 2007.

According to some embodiments, the capsule device is configured to havea specific gravity (SG) larger than 1 when the device resides in thestomach. For example, the capsule device SG is about 1.1, or between 1.1and 2. After the capsule device passes through the small bowel andenters the cecum, it must traverse the ascending colon. The capsuledevice SG is reduced to less than 1 (e.g., about 0.94) by the time itreaches the ascending colon. By reducing the SG the procedure timeshould not unnecessarily be prolonged so that patient does not need tofast for too long. Furthermore, the battery life for the capsule deviceis limited. If the capsule device stays in the ascending colon for toolong, the battery may be exhausted before the capsule device finishesits intended tasks, such as capturing images of the colon. Therefore, itis preferred that the capsule device has a specific gravity less than 1by the time it reaches the cecum or ascending colon. For example, thecapsule device may have an SG of about 0.94 or less. During theintermediary period between the stomach and large intestine the capsuledevice may have a SG of less than or greater than 1. In someembodiments, the capsule device may evolve into a first state with aspecific gravity greater than 1 when the capsule device resides in thestomach; the capsule device then evolves into a second state with aspecific gravity less than 1 by the time the capsule device reaches theascending colon; and the capsule device further evolves into a thirdstate with a specific gravity greater than 1 or with a density heavierthan the liquid by the time it reaches the descending colon. Finally thecapsule device will reach the anus for excretion. An SG of about 1.1 orlarger may be selected for the stomach and descending colon and aspecific gravity of 0.94 or smaller may be selected for the ascendingcolon. The embodiments of a deformable member where the SG slowerchanges based on the rates of diffusion of gas or liquid is an exampleof an evolving SG capsule device.

FIGS. 2A through 2D depict a capsule device 120 including a deformablemember 140 tethered to the housing 10 of the sensing system 110 (FIG.1).

FIG. 2A depicts an assembled view showing the capsule device 120 priorto being encased or encapsulated within a shell 130 configured totransport the device 120 to a target region of the GI tract, e.g., thestomach or the duodenum. The deformable member 140 includes a pouch 141formed from a semi-permeable or porous membrane 222, an effervescent 224contained within an interior of the pouch 141 and a tether 144connecting the pouch 140 to the housing 10. The tether 144 is secured toa loop 146 disposed at an end 10a of the housing 10.

FIG. 2A depicts the capsule device before the deformable member 140expands in response to the effervescent 224 being exposed to bodyliquid. The pouch 140 interior space is sealed from its exteriorenvironment, thereby allowing a fluid to pass in/out of the pouchinterior only through diffusion through its membrane 222 (an assembly ofthe deformable member 140 is discussed in connection with FIGS. 4Athrough 4E).

FIG. 2B shows the capsule device 120 within a biodegradable shell 130,which may be water soluble or enteric. The shell 130 has a front pieceor portion 130a shaped to form a space for the deformable member 140′.The folded pouch 141′ is packed within this open space provided at thefront piece/portion 130a of the shell 130. The shell 130 may be made intwo pieces (i.e., a front piece 130a and rear piece 130b) that aresecured together and may be coated by a water soluble, enteric orenzymatic coating 131.

The shell 130 may be made such that it adds significant additionalweight to the capsule device to effectively increase the net SG of thecapsule device and shell; or ballast may be included within the shellwith the capsule device. In either case, the increased SG can befavorable for reducing transit time through the stomach. After the shelldissolves this additional weight is lost.

In the case of the shell 130 being made from an enteric material, whenthe shell and capsule device of FIG. 2A approach the terminal ileum orthe cecum, the shell 130 has substantially or entirely dissolved due tothe higher pH level. At this point body liquid begins to diffuse throughthe porous material 222 and enters the pouch 141 interior space. Asdepicted in FIG. 2C, the diffused body liquid reacts with theeffervescent 224 therein to produce CO2. Although a small amount of bodyliquid resides in the pouch interior, the net effect of the reactionincreases the volume of the pouch 140 to a greater extent than the addedpouch weight brought on by the body liquid. As a result, the SG of thedevice in FIG. 2C is less than the SG of the device in FIG. 2A.

FIG. 2D depicts the state of the device 120 after all or most all of theeffervescence has taken place and the CO2 has diffused out of the pouch141. For example, after about 4 to 12 hours from the start of thereaction producing CO2 the pouch 141 interior contains mostly butlimited amounts of water 230 from body liquids, which results in a smallincrease in the device 120 SG. Eventually the device 120 SG returns tothe SG it had prior to the capsule device being placed in the shell 130.

In some embodiments the pouch 140 may be rectangular when deployed, asin the case of FIG. 2C. In other embodiments the pouch may beelliptical, e.g., circular, so that when it inflates with CO2 the pouchhas more rounded corners. In some embodiments the pouch 140 may bedesigned to be more of a hat or a sock on the housing, such as theembodiments described in connection with FIGS. 8A-8C. In someembodiments the shell 130 may completely encapsulate a sensing deviceand deformable member, or only a portion of the sensing device so as toallow the sensing device to acquire data prior to the deformable memberbeing exposed to body liquid. Any combination of these embodiments iscontemplated.

With reference to FIGS. 3A through 3B there is depicted a capsule device122 including a deformable member 150 tethered to the housing 10 of asensing system 112 according to another embodiment. FIG. 3A depicts thedevice 122 with a dome 132 (shown in cross-section) encapsulating thedeformable member 150 but not the entire sensing system 112. A sensingsystem according to this embodiment may be the same as that describedfor the capsule endoscope in U.S. Pat. No. 8,636,653 (the '653 patent).Referring to the '653 patent, in FIG. 2A there is shown a field of view(FOV) defining an imaging region 212, which is directed radiallyoutward, as opposed to forwardly with respect to the axis A in FIG. 3A.The shell 130 that encloses the entire device (FIG. 2B) would preventimages from being gathered until the shell 130 has dissolved, since theshell 130 blocks or obscures the FOV for an capsule endoscope configuredas in the '653 patent.

Referring to FIG. 3A the sensing system 112 radially-outwardly directedFOV is indicated by the shaded area 115. The dome 132 (enclosing afolded deformable member 150′) is sized to not obstruct this FOV for thesensing system 112. By the dome 132 not covering the FOV it is possiblefor the capsule device 122 to gather images before the dome 132 hasdissolved. The dome has a bulbous shape such that the radius ofcurvature of the bulbous dome may be greater than a radius of curvatureof the housing surface it covers. The dome 132 has a straight orcylindrical shaped end 133. The dome 132 may be secured in place by abiodegradable adhesive applied between the end 133 and surface of thehousing 10. The dome may alternatively have about the same radius ofcurvature as the housing surface it covers. In this case the dome 132may have an elongated cylindrical section 133 sized to provide the spacebetween the inner dome surface and housing surface 10 for the foldeddeformable member 150′.

Referring to FIG. 3B there is shown the deformable member 150 after thedome 132 has dissolved and the effervescent 224 begins to react with thediffused body liquid. The pouch 151 is shaped as an ellipse, which maybe preferred over the rectangular-shaped pouch 141 from FIG. 2B.

By its construction the pouch 140 when at full inflation may tend toform a cylindrical volume but with the seams extending around itsperimeter. In the case of the elliptical-shape pouch, the inflated shapemay to take the form of a spheroid having the seams. In otherembodiments the pouch 140 or 150 may be formed (at least in-part) by ablow-molding or injection molding process, in which case the pouch maymore resemble a cylindrical shape or spheroid, respectively.

FIGS. 4A through 4E depicts an assembly of the deformable member 140. Inthis example a length of 30 mm is chosen for the tether 144. Andmembrane material of 60×11 mm selected for the pouch 141 (FIG. 4A). Themembrane 222 is folded over to make the 30×11 mm size for the pouch 141(FIG. 4B). Three sides 147 of the membrane 222 are secured together(FIG. 4C), e.g., by heat seal. The effervescent 224 is added to thepouch 141 (FIG. 4D). The pouch 141 is evacuated of air and heat sealedon the open side 147a, to produce the deformable member 140 of FIGS.2A-2D. To make the pouch of FIG. 3B a membrane 222 may be cut to have aconnected pair of ellipse shapes, so that when folded at the connectionpart the pouch shape takes the form shown in FIG. 3B.

With reference to FIG. 5 there is a graph depicting inflation anddeflation periods for two types of capsule devices called Embodiment Aand Embodiment B, respectively. The Embodiments A and/or B maycorrespond to any of the illustrated embodiments of a capsule devicehaving deformable members 140 or 150. The solid curves refer to aninflation percentage (verses time) and the dashed curves refer to thechange in SG for the Embodiments A and B, respectively. In these graphsthe SG values of 0.94 and 1.1 are provided only as examples. As notedearlier, the upper end of SG may be up to 2 and the lower end may be aslow as 0.8. Moreover, the inflation percentage (80% and 100%) isexemplary only. In some embodiments the pouch may be constructed so thata desired lower end for SG is reached at only about 70%, or 75%inflation.

TABLE 1A, below, provides one example of a capsule device having thecharacteristics of Embodiment A. In this example the capsule device hasno enteric coating, nor does it have a shell or dome made form anenteric material. Thus, the deformable member of Embodiment A becomesexposed to body liquid relatively soon after the capsule is swallowed,e.g., within 5-30 minutes after being swallowed. According to EmbodimentA the deformable member may become exposed to body liquid while thecapsule resides in the stomach. Capsule devices according to EmbodimentA, which are configured for use without an enteric coating, or entericshell or dome, have a deformable member that inflates more slowly thancapsule devices encapsulated within an enteric coating or material.Embodiment B, in contrast, has a faster rise time. In the preferredembodiments the balloon is configured so that when it reaches about 80%inflation the capsule SG is equal to or less than 1.

TABLE 1A (Embodiment A) Time Approximate point/ time after Approximateinterval swallowing location for FIG. 5 (hours) patients Comment T0 n/aMouth Capsule SG >1; camera capsule with attached ouch encased insoluble sphere or dome T1 5-30 min Stomach Outer sphere or domedissolved and camera capsule with attached pouch comes in contact withbody fluids. Capsule SG starts to decrease as water permeates the pouchand initiates reactions with effervescent within. CO2 is generated. T21-4 hours small Capsule SG becomes <1 and intestine enough CO2 gas hasbeen produced to make the device bouyant. T1 ≤ 1-4 hours* n/a CO2 gasgeneration is slow t ≤ T2 enough to prevent the device from becomingbouyant and trapped in the stomach T3 n/a Large Capsule SG <1; SG islowest, intestine CO2 volume and gas pressure as gas diffuses throughmembrane wall faster than it is produced. T4 3-15 hours Large Capsule SGbecomes >1; CO2 intestine gas has diffused through membrane wall and thedevice is no longer bouyant T2 ≤ 4-12 hours* n/a Capsule SG <1; Deviceis t ≤ T4 bouyant and SG is below 1 for at least 4 hours to make surethe device transits well from small intestine to lage intestine. T5 4-25hours Excreted or >90% of the generated CO2 gas in large has diffusedout of the pouch intestine *Does not reflect the times from swallowingthe device

TABLE 1B (Embodiment B) Approximate Approximate Time- time afterlocation point swallowing for most FIG. 5 (hours) patients Comment T0n/a Month Capsule SG >1; camera capsule with attached pouch encased insoluble sphere or dome T1 10 min- Small Outer sphere or dome w euteric 3hours intestine or time controlled coating dissolved and camera capsulewith attached pouch comes in contact with body fluids. Capsule SG startsto decrease as water permeates the pouch and initiates reaction witheffervescent within and CO2 starts to be generated. T2 30 min- SmallCapsule SG becomes <1 and 3.5 hours intestine enough CO2 gas has beenproduced to make the device bouyant. T1 ≤ 5 min- n/a CO2 gas generationcan be fast t ≤ T2 1 hour as the device is already in small intestineand the risk that the device becomes bouyant and trapped in the stomachis low. Allows for thinner pouches. T3 n/a Large Capsule SG <1; SG islowest. intestine CO2 volume and gas pressure at highest and begins todecrease as gas diffuses through membrane wall faster than it isproduced T4 3-15 hours Large Capsule SG becomes >1; CO2 intestine gashas diffused through membrane wall and the device is no longer bouyant.T2 ≤ 2-15 hours* n/a Capsule SG <1; Device is t ≤ T4 bouyant and SG isbelow 1 for at least 2 hours to make sure the device transits well fromsmall intestine to large intestine. T5 4-25 hours Excreted or >90% ofthe generated CO2 gas in large has diffused out of the pouch intestine*Does not reflect the times from swallowing the device

TABLE 1B, below, provides one example of a capsule device having thecharacteristics of Embodiment B. In this example the capsule device hasan enteric or time-controlled coating, or has a shell or dome made froman enteric or time-controlled material. Thus, the deformable member ofEmbodiment B becomes exposed to body liquid after the capsule has passedthrough the pyloric valve. According to Embodiment B the deformablemember does not become exposed to body liquid until the capsule reachesthe small bowel (Once the enteric or time-controlled coating hasdissolved the body fluid dissolvable shell or dome dissolves quickly).Capsule devices according to Embodiment B have a deformable member thatinflates more quickly than capsule devices encapsulated without anenteric or time-controlled coating or material (Embodiment A). Referringonce again to FIG. 5, the different curves and/or slopes of curves forthe pouch inflation pressure vs. time, and/or percent inflation for atarget SG to achieve buoyancy, may be arrived at by varying parametersaffecting the inflation rate and duration for the pouch when exposed tobody liquid. These parameters may include one or more, or anycombination of the following parameters (a) through (i):

-   -   (a) The amount (by weight or volume) of effervescent in the        pouch. In one embodiment between about 1 and 100 milligrams, and        more preferably between about 5 to 50 milligrams of an        effervescent comprising a bicarbonate salt an anhydrous acid or        preferably, sodium bicarbonate, and/or potassium bicarbonate,        and anhydrous citric acid is used. In a preferred embodiment the        effervescent is composed of about 20% by weight of sodium        bicarbonate, about 40% by weight of potassium bicarbonate, and        about 40% by weight anhydrous citric acid.    -   (b) Coarse or fine granules of effervescent or an effervescent        tablet. And/or aged or fresh granules of effervescent or an        effervescent tablet.    -   (c) The amount of desiccant in the pouch vs. effervescent. In        one embodiment a ratio of between about 1:25 and 1:0.04 of        desiccant to effervescent, and more preferably between about        1:10 and 1:0.1 of desiccant to effervescent is used. In a        preferred embodiment polyethylene glycol is used as a desiccant        and the ratio of effervescent to this desiccant is 0.5 to 2, or        1 to 1. A preferred molecular weight of the polyethylene glycol        is in the range of 5,000 to 50,000 Daltons with a linear, 4- or        8-armed star structure.    -   (d) The presence of a coating over the effervescent, e.g., an        enteric coating or water soluble coating. In some embodiments it        may be desirable to coat the effervescent material with a        coating so as to obtain a more controlled release of CO2. The        effervescent may be coated with an enteric coating, to be used        in combination with a shell or dome that dissolves in the        stomach. In some embodiments it may be desirable to have the        effervescent placed in contact with the membrane of the        deformable member so that body liquid diffused through the        membrane will reach and react with the effervescent material as        quickly as possible. In other embodiments it may be unnecessary        or undesirable to place the material in contact with the        membrane because it is desirable to delay the reaction time for        reasons previously given above.    -   (e) The pouch size. In one embodiment a rectangular pouch has        dimensions of about 30×11 mm or about 2×330 mm² surface area        total surface area for the outer surface of membrane material. A        rectangular pouch (FIG. 2A) may have a ratio of length to width        of 2:1, 1:1, or 3:1, or between 2:1 to 3:1 for the membrane. The        pouch may alternatively have an elliptical shape (FIG. 3B). In        the embodiments the total external surface area of the pouch        (representative approximately of its internal volume capacity        when under pressure) is between 50 and 1,500 mm² and more        preferably between 300 and 1,000 mm².    -   (f) The membrane wall thickness. The wall thickness can range        from between 0.2 to 10 mils (about 5 to 254 microns) and more        preferably 0.5 to 5 mils (about 12 to 125 microns).    -   (g) The membrane may be made from any of the following, or        combinations of material: polyetherblockamide copolymers,        thermoplastic polyurethanes, polyamides, polyamide block        copolymers, polyamide elastomers, polyurethanes, polyesters,        polyester copolymers, polyamide copolymers, polyurethane        copolymers, polyether copolymers, polyesteramides,        polyesteramide copolymers, polyvinyl chloride, polyvinyl        chloride copolymers, polyvinylidene dichloride, polyvinylidene        dichloride copolymers, fluoropolymers, polyvinyl fluoride,        polyvinyl fluoride copolymers, polyvinylidene difluoride,        polyvinylidene difluoride copolymers, polyvinylpyrrolidone        copolymers, polyvinylalcohol copolymers, two layered, three        layered, or multi layered films of various materials may be used        to provide a combination of barrier properties from one material        and mechanical or adhesive properties for sealing of another.        Pouches may also have one material on one side and another        material on the other or opposite side. The membrane material        may be present on the entire side, or only a portion of one        side, or only exposed on a portion of one side or both sides.        Additionally, the membrane composition may be varied by        thickness, polymer type, layering of different or the same        material, or by change of patterning.    -   (h) An enteric, enzymatic, time-controlled (water soluble), or        body fluid-soluble (water-soluble, non-enteric) coating.    -   (i) An enteric, enzymatic, time-controlled (water soluble), or        body fluid-soluble (water-soluble, non-enteric) shell or dome.

With respect to parameter (a), the more effervescent material in thepouch, the more CO2 gas is available for inflating the pouch. The amountof effervescent chosen may be based on the desired amount and durationof buoyancy for the capsule. For example, referring to FIG. 5 theduration of time for Embodiment A at or above 80% inflation covers theperiod T2 to T4. During this time the capsule has an SG no greaterthan 1. Thus, for this embodiment it can be expected that the capsulewill float in the body liquid from T2 to T4. If a greater amount ofeffervescent is added the duration of time where SG is less than 1 mayincrease.

With respect to parameter (b), the coarseness of the effervescentparticles, or choice of a tablet over particles for the effervescent maychange the reaction times, e.g., production of CO2 at a quicker ratewhen finely ground effervescent particles are used in place of a tabletdue to the increased surface area. In current testing however it wasfound that the size of the effervescent granules, or choosing a granuleover a tablet did not produce much change in the curves of FIG. 5.

With respect to parameter (c), the addition of desiccant to the pouchcan significantly delay or reduce the rate of CO2 production in thepouch, because the desiccant will adsorb water, or absorb waterdepending on the desiccant used (both types are contemplated for use).Accordingly, by using a greater percentage of desiccant material (inproportion to effervescent) the rise time for pouch inflation can beincreased. For example, all other parameters being equal betweenEmbodiments A and B, the Embodiment A curve (FIG. 5A) may be achieved byadding more desiccant to the pouch of Embodiment B (FIG. 5B), therebymaking the rise time longer for Embodiment A than Embodiment B. A slowerrise time is preferred for a shell, dome or coating that dissolves inthe stomach.

Thus, with respect to parameters (b) and (c), the addition of desiccantinside the pouch will adsorb (or absorb) the water from the body liquidand delay production of CO2 and the coarseness of the desiccantparticles, or choice of a tablet over particles for the effervescentcombined with the desiccant may change the reaction times, e.g.,production of CO2 at a slower rate when finely ground and well mixed asa powder or tablet effervescent and desiccant particles are used inplace of a more coarse or less well mixed mixture due to the increasedsurface area.

With respect to parameter (d), the coating on the effervescent particle(or tablet) may prevent or delay the body liquid mobilization of theeffervescent material and therefore may delay the production of CO2until the right time or the pH has changed. The coating thus caneffectively reduce the rate of CO2 production within the pouch andincrease the rise time. In some embodiments an effervescent has anenteric coating. Other embodiments use instead a coating designed todissolve in the stomach or small bowel within about 2-4 hours afterbeing in contact with body fluids, unless they are enteric, in whichcase they will not dissolve in the low pH of the stomach butdisintegrate in the higher pH environment of the small bowel or colon.The coating may be made of polymers, polysaccharides, plasticizers,methyl cellulose, gelatin, sugar, or other materials.Hydroxypropylcellulose, hypromellose acetate succinate and methacrylicacid co-polymer type C are examples of an enteric polymer. Thesematerials may also be applied as coatings to the deformable member aloneor to it and the sensing system. For example, all other parameters beingequal the Embodiment A curve (FIG. 5A) may be achieved by using anon-coated effervescent, while using a coated effervescent material maydelay the onset of T1 from being in the stomach to being in the smallbowel (Embodiment B, FIG. 5B) or if time controlled may delay it from 20min after swallowing to 2-4 hours after swallowing. A delayed T1 ispreferred for a shell or dome that dissolves in the small intestine. Italso allows the use of thinner balloon materials.

With respect to parameter (e), pouch sizes may be limited to ensure thatit does not get caught on any anatomy when the pouch becomes inflated,e.g., if the pouch were to achieve near 100% inflation prior to reachingthe cecum. A smaller pouch size for the same amount of effervescentshould produce a higher gas pressure, which may increase the rate ofdiffusion of gas from the membrane. In some embodiments a morenon-compliant membrane is used, as a measure for controlling the volumeof the inflated pouch. A compliant membrane material may be used, as ameasure for controlling internal pressure. A less or more compliantmembrane material may be understood as a membrane having a lower orhigher wall thickness, respectively, or a lower or higher elasticmodulus in general.

With respect to parameters (f) and (g), the pouch membrane material andwall thickness can affect the rate of diffusion of body liquid (water)into the pouch interior and as a result the rate of CO2 production,parameters (f) and (g) also affect diffusion of CO2 gas out of thepouch. For example, if the membrane wall thickness is increased, therate at which body fluid diffuses into, and/or CO2 gas diffuse out ofthe pouch interior should decrease. As will be appreciated from theforegoing, this effect may be somewhat different if, for example, at thesame time the amount of effervescent used per unit volume of the pouchinterior is increased or decreased. If there is more gas produced perunit volume the pouch internal gas pressure should increase, which maydecrease the diffusion of body fluid into the pouch thereby increasingthe buoyancy period and/or increasing the rise time.

Similarly, for a higher wall thickness the deflation period (e.g., fromT4 to T5 in FIG. 5B) should increase. An increase or decrease in thesurface area of the pouch may be thought of as having a similar effectas a decrease or increase, respectively, in the effervescent per unitvolume. For example, for an increase in the surface area with noincrease in the amount of effervescent used the rise time shoulddecrease.

With respect to parameters (h) and (i), embodiments of a capsule devicehave an enteric coating, or shell or dome made from an enteric material,or the capsule device may be coated with an enteric, enzymatic,time-controlled (water soluble), or body fluid-soluble (water-soluble,non-enteric) coating, or use shells or domes devoid not made from anenteric material. FIGS. 5A and 5B and Tables 1A and 1B illustrate thesedifferences. The foregoing selection of appropriate parameters toachieve a desired inflation rate may be guided substantially by whetheror not an enteric coating or material is used. Embodiments of coatings,domes or shells are designed to dissolve in the stomach or small bowelwithin about 30 minutes of swallowing, unless they are enteric, in whichcase they will not dissolve in the low pH of the stomach butdisintegrate in the higher pH environment of the small bowel or colon.The shell or dome may be made of polymers, polysaccharides,plasticizers, methyl cellulose, gelatin, sugar, or other materials.Hydroxypropylcellulose, hypromellose acetate succinate and methacrylicacid co-polymer type C are examples of an enteric polymer Thesematerials may also be applied as coatings to the deformable member aloneor to it and the sensing system. There may be reasons for using one typeof dome, coating or shell over another depending on the type ofapplication. On the one hand a shell configured to dissolve in thestomach is reliable and should not depend too much on the patient'scondition. On the other hand, there may be concern over whether thepouch inflates too soon and before the capsule has passed through thestomach. In this case the capsule may not exit the stomach and insteadfloat in the stomach.

An enteric shell or an enteric coated shell should not dissolve fullyuntil the capsule has reached the small bowel. Thus, the pouch shouldideally not start to inflate until after the capsule has passed throughthe stomach. The advantage here is the pouch may inflate rapidly and theonly possible limitation or challenge may be to keep pouch inflated longenough to stabilize its transit through the ascending colon as well asthrough the transverse colon. Another advantage is that more typesand/or thinner pouch materials may be used. And there is less need fordesiccants. However, an enteric shell or coating can be expensive andmore sensitive to changes in pH. Thus, the enteric shell may not fullydissolve in the small bowel unless the pH level is sufficiently high,which can make its effectiveness more dependent on a particularpatient's condition. Should the shell not dissolve, the pouch cannotinflate and the capsule will not ascend the colon.

Thus, when choosing between an enteric shell, dome or coating verses onethat is dissolved by gastric juices, one may select a pouchconfiguration that has a slower rise time when the shell, dome orcoating dissolves in the stomach. And when an enteric shell, dome orcoating is used the rise time can be decreased. There may be advantagesor disadvantages, and/or other factors to consider. For instance, aconfiguration that yields a slower rise time may also take longer todeflate, which can result in unacceptable delay in getting the capsulethrough the transverse and descending colon due to its low SG. Thisproblem may be overcome by using a relatively thin wall thickness, sincetests show that the deflation time is mostly a function of the wallthickness of the membrane.

Testing

Bench tests were conducted to evaluate changes in buoyancy periods for avariety of pouch configurations. The tests varied the amount ofeffervescent material, the pouch material, pouch wall thickness anddimensions, as well as the type and amount of desiccant. The apparatusused to test pouch properties consisted of a pouch (assembled as shownin FIGS. 4A-4E) suspended from an arm coupled to a weighing scale. Thearm overhung a basin of water heated to about 37° C. Ballast wasattached to the pouch. The weight of the suspended pouch and ballastwere recorded (dry weight). Next, the pouch and ballast and were droppedinto the water. The change in weight of the pouch and ballast were thenrecorded over the next 10 to 20 hours.

As the reaction between the water and effervescent takes place, the SGof the pouch and ballast changed: the SG decreased (CO2 produced fromthe reaction between the water and effervescent), the SG reached aminimum value (corresponding to a 100% inflation condition), and thenthe SG increased as CO2 diffused from the pouch.

FIG. 6 is a normalized plot showing changes in pouch inflation volumeover time among six different configurations of a pouch from the benchtests. The ordinate refers to the percentage change in inflation for thepouch where 100% inflation means the highest amount of inflation or gaspressure achieved within the interior of the pouch. The test article foreach of the six test samples depicted in FIG. 6 (labeled as “Exp 1”,“Exp 2”, “Exp 3”, “Exp 4”, “Exp 5” and “Exp 6”) are summarized below:

Exp 1: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used(fine grind, aged).

Exp 2: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mm of effervescent used(fine grind, aged).

Exp 3: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used(fine grind, fresh).

Exp 4: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used(fine grind, fresh).

Exp 5: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used(coarse grind, fresh).

Exp 6: a pouch membrane was made from PEBAX 4 mils and with dimensions30×11 mm, wall thickness 4 mil (0.1 mm), and 20 mg of effervescent used(coarse grind, fresh).

FIG. 7 shows additional results from tests. Listed are the materials andsize and wall thickness of the pouch. The amount of effervescent usedwas varied from between 5 mg to 30 mg and was either coarse or fine, andaged or new. The “n” vales refer to the number of experiments performed.The data under the columns Ta, Tb, Tc, Td, Te and Tf are explained below(time “T0” refers to the moment when the pouch is placed in the water).These times are given in units of hours.

Ta is the time elapsed from T0 to when the pouch reaches 80% inflation.

Tb is the time elapsed from T0 to when the pouch reaches 100% inflation.

Tc is the time elapsed from T0 to when the pouch inflation begins todecrease from a 100% inflation state.

Td is the time the pouch maintains 100% inflation; thus, Td=Tc−Tb.

Te is the time elapsed from T0 to when the pouch inflation begins todecrease from a 80% inflation state.

Tf is the time the pouch maintains 80% inflation; thus, Tf=Te−Ta.

In some cases the pouch did not reach 100% inflation or 80% inflation.These are noted in the comments. In some cases the rectangular-shapedpouch was modified to have a double seal or a double bag. A double sealmeans there was an inner rectangular seal made in the bag, in additionto the outer seal. A double bag means the effervescent was placed in asealed inner bag, and then the inner bag was placed in a sealed outerbag.

The parameters that have the most significant effects on theinflation/deflation periods reported are the type of polymer, wallthickness, type and amount of desiccant, and quantity of effervescentmaterial in the pouch. When more effervescent was used, the rise timedecreased and the period above 80% inflation increased. An increase ineffervescent material used, however, can also significantly increase thedeflation time.

The following discloses additional embodiments of a capsule device.

FIGS. 8A-8C depict an example of a capsule device with a deformablemember 220 integral with the housing 10 of the sensing system 110. As inprior embodiments the device includes a pouch 221 formed from asemi-permeable membrane material 222, and an effervescent 224 containedwithin an interior of the pouch 221. One difference between this capsuledevice and previously discussed embodiments is that the deformablemember 220 is integral with the capsule housing 10, as opposed to beingtethered to it. The membrane material 222 chosen may be more elasticthan in prior embodiments since ends of the pouch 221 is constrained tothe relatively rigid surface of housing 10 and thus less able toincrease its interior volume as in prior embodiments without stretchingof the membrane. The membrane material 222 may be attached to thesurface of the housing 10 by an adhesive so that a fluid-tight interiorto the pouch 221 is formed. As such, body liquid enters the interior ofthe pouch 221 only by way of diffusion through pores of the membrane222.

FIG. 8A depicts a capsule device before the deformable member 220expands in response to the effervescent 224 being exposed to bodyliquid. The effervescent 224 is contained within the interior of thepouch 221 made of the porous or semi-permeable membrane material 222.

In this particular embodiment an enteric coating 223 (as represented bydashed lines) is applied to the exterior of the membrane 222 to preventdiffusion of body liquid into the pouch interior until after the capsuledevice has entered the small intestine. The enteric coating may alsocover the sensing device 110.

When the capsule device of FIG. 8A approaches the terminal ileum or thececum, the enteric coating 223 dissolves due to the higher pH level, asdepicted in FIG. 8B. With the enteric coating dissolved, body liquidbegins to diffuse through the porous material 222 and enters theinterior space. Thus, the reaction takes place producing the gas thatexpands the pouch volume, as shown in FIG. 8C. Although a small amountof fluid 230 resides in the pouch 221 interior, the net effect of thereaction increases the volume of the pouch to a greater extent than theadded pouch weight brought on by the body liquid. The SG of the devicein FIG. 8C is less than the SG of the device in FIG. 8A. In someembodiments it may be desirable to have the effervescent material 224placed in contact with the semipermeable membrane of the deformablemember so that body liquid diffused through the membrane will reach andreact with the effervescent material 224 as quickly as possible. Inother embodiments it may be unnecessary or undesirable to place thematerial 224 in contact with the membrane because it is desirable todelay the reaction time for reasons previously given above

FIGS. 8D-8E depict later stages of the capsule device of FIG. 8CCompared to the state in FIG. 8C, the state in FIG. 8D shows that morebody liquid has accumulated in the pouch 224 interior and less gas (as aresult of diffusion of the gas through the membrane 222). FIG. 8Edepicts a state of the capsule device after its SG has increased toabove 1 due to the amount of body liquid that has diffused into thepouch 224 interior.

FIGS. 9A-9B depict an example of a deformable member 320 integral withthe housing 10 (as in FIGS. 8A-8C). According to this embodiment thedeformable 320 includes a pouch 321 having the effervescent in itsinterior (FIG. 9A shows the pouch 321 configuration after body liquidhas diffused into its interior space and CO2 gas released). The pouch321 is formed by a membrane 322 that is permeable to body liquid andsubstantially impermeable to gas. A biodegradable relief valve, plug orseal made of a biodegradable (or resorbable) material 310 covers anopening in the membrane 322. The seal 310 may be configured to degradewithin a few hours of exposure to body liquid.

FIG. 9B depicts the state of the deformable member 320 after the sealhas degraded. The gas has been released and the SG of the capsule devicehas increases back to above 1. FIG. 10 depicts an embodiment of acapsule device where a housing 450 of the capsule device 400 includes aflexible section 430. For example, a bellows-like structure can be usedfor the flexible section. The flexible section can be expanded orcompressed along a longitudinal direction 440 of the capsule device 400.Furthermore, the capsule device 400 comprises sensor 410 and light 420for capturing images inside the body lumen.

FIGS. 11A and 11B depict an embodiment of a capsule device 500 where twocoupled parts 530 and 540 are biased to spring apart to form an enlargedvolume of the housing (FIG. 5B). The parts 530, 540 are held together bya biodegradable or resorbable seal. When exposed to body liquid the sealbreaks and the two parts move apart. With the increased volume and thehousing formed by parts 530, 540 moved apart and the housing beingliquid impermeable, the device 500 has a SG that decreases as the parts530, 540 move part. The housing may be maintained in a sealed (liquidimpermeable) condition by disposing an O-ring or gasket between theoverlapping sections of parts 530, 540. FIGS. 11A and 11B illustratestates where the capsule device has an SG greater than 1 and less than1, respectively.

FIG. 12 illustrates a capsule device 600 where a main sensor system 630is configured to accommodate an extendable attachment 640. Theextendable attachment 640 can be moved within a range indicated by 650.When fully extended (i.e., attachment 640 moved from left to right inFIG. 12) the capsule volume increases; hence the SG decreases.

The embodiments of FIGS. 10-12 illustrate examples of capsules with anexpandable housing. The housing may be expanded in these embodiments byan actuator such as a motor and screw drive internal to the housing.Such actuators may consume excessive power, however. Another option isto spring load the housing internally. The housing expansion may beconstrained by an external biodegradable shell or coating that dissolvesafter the capsule device is swallowed.

In one or more of the aforementioned other embodiments a capsule devicemay be coated with a material to decrease drag or friction between thehousing and body liquid, or anatomy encountered in the GI track.Hydrophilic coatings are one example of a coating that may be used tocoat the capsule's housing surface.

In a wireless application, a transmitter is used to transmit image datato a receiver system external to the body and the image data is storedin an external recorder. In U.S. Pat. No. 5,604,531, a wireless capsulesystem is disclosed and the capsule system with a wireless transmitteris powered by the battery within the capsule. For colon applications,the transit time is substantially longer than for small bowelapplications. Therefore, the receiver system and external recorder maybecome burdensome to carry over long hours (e.g., 10 hours or more).Since the time period for a colon application in general takes longerthan, e.g., 8-10 hours, an out-patient procedure would require thepatient to bring the receiver/transceiver equipment with him or her.This increases healthcare costs since additional (portable) equipment isneeded to gather data for the colon. Additionally, the signalstransmitted/received between the device and receiver can interfere withnearby equipment, such as another implant. It may therefore be preferredto utilize for colon applications a capsule device that can travelthrough the large intestine more rapidly. This may be achieved by havingthe SG return back to an SG greater than 1 after the capsule has passedthrough the ascending colon, by use of an booster protocol, or acombination of the two. In yet another embodiment of the presentinvention, the density control means is applied to a capsule system withon-board storage. Such system is disclosed in to U.S. Pat. No.7,983,458, entitled “in vivo Autonomous Camera with On-Board DataStorage or Digital Wireless Transmission in Regulatory Approved Band”,granted on Jul. 19, 201. The capsule system with on-board storage doesnot require the patient to wear any external equipment. Therefore, thecapsule system with on-board storage is much preferred for procedurerequiring a prolonged time period. Furthermore, in PCT PatentApplication No. PCT/US13/42490, a docketing station to read out archiveddata from a capsule system with on-board storage is disclosed. Thecapsule system comprises a set of probe pads disposed on the housing.After the capsule device is excreted and recovered, the image data canbe retrieved by probing these probe pads without opening the capsulehousing. Since the battery power is pretty much depleted when thecapsule device is retrieved, one pair of the probe pads can be used toprovide power and ground for the data retrieval operation.Alternatively, the power can be provided using inductive powering asdisclosed in PCT Patent Application Series No. PCT/US13/39317. After thecapsule is recovered, the data may be transmitted optically through atransparent portion of the capsule to an external receiver.

The following additional Concepts are included as part of the foregoingdisclosure.

Concept 1. A capsule device, comprising: a sensor system comprising: alight source; an image sensor for capturing image frames of a sceneilluminated by the light source; an archival memory; and a housingadapted to be swallowed, wherein the light source, the image sensor andthe archival memory are enclosed in the housing; and a density controlmeans for causing at least two specific gravities of the capsule devicefor at least two designated regions of gastrointestinal trackrespectively, wherein each of said at least two specific gravities isselected from a first group consisting of a greater-than-one state and aless-than-one state.

Concept 2. The capsule device of Concept 1, wherein the greater-than-onestate correspond to the specific gravity of about 1.1 or larger and theless-than-one state corresponds to the specific gravity of about 0.94 orsmaller.

Concept 3. The capsule device of Concept 1, wherein said at least twodesignated regions of the gastrointestinal track are selected from asecond group comprising stomach, ascending colon and descending colon.

Concept 4. The capsule device of Concept 1, wherein said at least twodesignated regions of the gastrointestinal track correspond to stomachand ascending colon, and wherein the corresponding said at least twospecific gravities are the greater-than-one state and the less-than-onestate respectively.

Concept 5. The capsule device of Concept 1, wherein said at least twodesignated regions of the gastrointestinal track correspond to stomach,ascending colon and descending colon, and wherein the corresponding saidat least two specific gravities are the greater-than-one state, theless-than-one state and the greater-than-one state respectively.

Concept 6. The capsule device of Concept 1, wherein whether the capsuledevice is located in or approaching at one of said at least twodesignated regions of the gastrointestinal track is determined based on:estimated transit time after the capsule device is swallowed; pH valuesmeasured at capsule device locations; luminal pressure measured at thecapsule device location; identification of image contents based oncaptured images by the capsule device; motion detection based on thecaptured images by the capsule device; colonic microflora detected atthe capsule device location; or estimation of lumen diameter.

Concept 7. The capsule device of Concept 1, wherein said density controlmeans couples a deformable member to the sensor system, wherein thedeformable member contains gas generating material, said density controlmeans causes the deformable member to inflate by causing fluid to enterthe deformable member so that the gas generating material generates gasand the capsule device has the specific gravity less than one.

Concept 8. The capsule device of Concept 7, wherein the deformablemember is coated with an enteric coating before the capsule device isswallowed to prevent the fluid to enter the deformable member before thecapsule device exits stomach.

Concept 9. The capsule device of Concept 7, wherein the deformablemember comprises a biodegradable plug, wherein the biodegradable plugbecomes separated or partially separated from rest of the deformablemember or causes leaks on the deformable member to let the gas and thefluid to leak from the deformable member.

Concept 10. The capsule device of Concept 7, wherein the deformablemember is made of a first material which is more permeable to the gasthan to the fluid.

Concept 11. The capsule device of Concept 10, wherein the deformablemember inflates with the gas and later deflates as the gas diffuses outof the deformable member faster than the fluid diffuses in thedeformable member.

Concept 12. The capsule device of Concept 7, wherein after a firstperiod of time since the capsule device reaches the specific gravityless than one, the density control means causes the capsule device toreach the specific gravity greater than one by allowing the fluid tocontinue to enter the deformable member such that a volume ratio of thegas to the fluid inside the member decreases.

Concept 13. The capsule device of Concept 1, wherein the capsule deviseis coated with or made of a second material so that the capsule devisehas a reduced friction with body lumen or fluid.

Concept 14. The capsule device of Concept 1, wherein electrical contactsare disposed fixedly on the housing, wherein the electrical contacts arecoupled to the archival memory so that an external device is allowed toaccess image data stored in the archival memory through the electricalcontacts.

Concept 15. The capsule device of Concept 14, wherein the electricalcontacts include power pins to provide power to the capsule device fordata retrieval of image data stored on the archival memory.

Concept 16. The capsule device of Concept 14, wherein inductive poweringis used to provide power to the capsule device for data retrieval ofimage data stored on the archival memory.

Concept 17. The capsule device of Concept 1, wherein the capsule devicefurther comprises: an optical transmitter to transmit an optical signalthrough a clear window, wherein image data from the archival memory istransmitted to an external optical receiver.

Concept 18. The capsule device of Concept 17, wherein inductive poweringis used to provide power to the capsule device for data retrieval ofimage data stored on the archival memory.

The above description of illustrated embodiments of the invention,including what is described in the Abstract, is not intended to beexhaustive or to limit the invention to the precise forms disclosed.While specific embodiments of, and examples for, the invention aredescribed herein for illustrative purposes, various modifications arepossible within the scope of the invention, as those skilled in therelevant art will recognize.

These modifications can be made to the invention in light of the abovedetailed description. The terms used in claims should not be construedto limit the invention to the specific embodiments disclosed in thespecification.

What is claimed is:
 1. A capsule endoscope, comprising: a sensor systemcomprising a light source, an image sensor for capturing image frames ofa scene illuminated by the light source; a housing adapted for beingswallowed, wherein the housing encloses the sensor system; and at leastone pouch containing an effervescent, the pouch being attached to thehousing and being semi-permeable or porous, permeable to body liquid butnot to gas so that the effervescent is able to generate gas upon contactwith the body liquid; wherein at least the pouch is encapsulated withina dissolvable shell, dome or coating, and wherein specific gravity (SG)of the capsule endoscope is greater than 1 when the pouch isencapsulated within the dissolvable shell, dome or coating and whereinthe SG of the capsule endoscope corresponds to a specific gravity of allthe components of the capsule endoscope collectively together; andwherein the capsule endoscope said at least the pouch is configured tocontrol estimated inflation and deflation periods of the capsuleendoscope said at least the pouch such that the capsule endoscope hasthe SG of the capsule endoscope greater than 1 for a first period oftime, and less than 1 for a second period of time following the firstperiod of time; and wherein the capsule endoscope said at least thepouch is configured to control estimated inflation and deflation periodsof the capsule endoscope said at least the pouch by properly selectingparameters from a parameter group comprising a combination of pouchmembrane type and pouch wall thickness to affect a rate of diffusion ofbody liquid into the pouch.
 2. The capsule endoscope of claim 1, whereinat least the pouch is encapsulated within an enteric shell, dome orcoating.
 3. The capsule endoscope of claim 2, wherein the enteric shell,dome or coating is designed to dissolve a pH in range of 5.0-7.4 so thatthe enteric shell, dome or coating is intended to disintegrate in thesmall intestine or the cecum.
 4. The capsule endoscope of claim 2,wherein the capsule endoscope is configured to cause the specificgravity (SG) of the capsule endoscope drops below 1 in about 2-6 hoursafter the capsule endoscope is exposed to bodily fluids by swallowingthe capsule endoscope.
 5. The capsule endoscope of claim 2, wherein theendoscope is configured such that the specific gravity (SG) of thecapsule endoscope is more than 1 for more than about six hours after thecapsule endoscope is exposed to bodily fluids by swallowing the capsuleendoscope.
 6. The capsule endoscope of claim 2, wherein the pouch has awall thickness of less than 2 mils for one a first group of pouchmaterials or less than 5 mils for another a second group of pouchmaterials.
 7. The capsule endoscope of claim 2, wherein the pouch isconfigured such that the specific gravity (SG) of the capsule endoscopeis more than 1 for more than 1.5 hours after the pouch is exposed tobodily liquids by swallowing the capsule endoscope.
 8. The capsuleendoscope of claim 2, wherein the pouch is configured such that thespecific gravity (SG) of the capsule endoscope is less than 1 for morethan 2 or 4 hours after the pouch is exposed to bodily liquids byswallowing the capsule endoscope.
 9. The capsule endoscope of claim 1,wherein the endoscope is configured such that the specific gravity (SG)of the capsule endoscope drops below 1 in about 2-6 hours after thecapsule endoscope is exposed to bodily fluids by swallowing.
 10. Thecapsule endoscope of claim 1, wherein the endoscope is configured suchthat the specific gravity (SG) of the capsule endoscope is less than 1for more than about six hours after the capsule endoscope is exposed tobodily fluids by swallowing the capsule endoscope.
 11. The capsuleendoscope of claim 1, wherein the pouch comprises is selected from a setconsisting of polyetherblockamide copolymers, thermoplasticpolyurethanes, polyamides, polyamide block copolymers, polyamideelastomers, polyurethanes, polyesters, polyester copolymers, polyamidecopolymers, polyurethane copolymers, polyether copolymers,polyesteramides, polyesteramide copolymers, polyvinyl chloride,polyvinyl chloride copolymers, polyvinylidene dichloride, polyvinylidenedichloride copolymers, fluoropolymers, polyvinyl fluoride, polyvinylfluoride copolymers, polyvinylidene difluoride, polyvinylidenedifluoride copolymers, polyvinylpyrrolidone copolymers, or andpolyvinylalcohol copolymers.
 12. The capsule endoscope of claim 1,wherein the pouch has a wall thickness of less than 5 mils or less than10 mils.
 13. The capsule endoscope of claim 1 12, wherein the pouchwater uptake in 12 hours relative to a pouch and effervescent dry weightis less than 200% for one a first group of pouch materials or 50% foranother a second group of pouch materials.
 14. The capsule endoscope ofclaim 13, wherein the pouch material is selected from a set consistingof polyetherblockamide copolymers, thermoplastic polyurethanes,polyamides, polyamide block copolymers, polyamide elastomers,polyurethanes, polyesters, polyester copolymers, polyamide copolymers,polyurethane copolymers, polyether copolymers, polyvinyl chloride,polyvinyl chloride copolymers, polyvinylidene dichloride, polyvinylidenedichloride copolymers, fluoropolymers, polyvinyl fluoride, polyvinylfluoride copolymers, polyvinylidene difluoride, or and polyvinylidenedifluoride copolymers.
 15. The capsule endoscope of claim 1, wherein theYoung's modulus of the pouch is: high enough to create a non-conformalpouch; or low enough to create a slightly conformal pouch, such that thepouch can reach a maximum size 25% above the nominal size with a maximumof 40 mg effervescent.
 16. The capsule endoscope of claim 1, wherein thepouch is configured such that the specific gravity (SG) of the capsuleendoscope is more than 1 for more than 1.5 hours after the pouch isexposed to bodily liquids by swallowing the capsule endoscope.
 17. Thecapsule endoscope of claim 1, wherein the pouch is configured such thatthe specific gravity (SG) of the capsule endoscope is less than 1 formore than 2 or 4 hours after the pouch is exposed to bodily liquids byswallowing the capsule endoscope.
 18. The capsule endoscope of claim 1,wherein the pouch is configured such that the specific gravity (SG) isof the capsule endoscope is less than 1 for more than 4 hours but lessthan 12 hours after the pouch is exposed to bodily liquids by swallowingthe capsule endoscope.
 19. The capsule endoscope of claim 1, wherein theeffervescent is coated.
 20. The capsule endoscope of claim 16 19,wherein the effervescent coating is an enteric coating designed to a pHin the range of 5.0-7.4 such that the effervescent is intended to reactwith water after the endoscope has reached the small intestine.
 21. Thecapsule endoscope of claim 1, wherein the pouch further comprises adesiccant.
 22. The capsule endoscope of claim 21, wherein the ratio ofdesiccant to effervescent is 1:10 to 2:1 by weight.
 23. The capsuleendoscope of claim 1, wherein the pouch has a total exterior surfacearea of about 300 and 1,000 mm².
 24. The capsule endoscope of claim 23,wherein between about 10 mg and 50 mg of effervescent are containedwithin the pouch.
 25. The capsule endoscope of claim 1, wherein specificgravity (SG) of the capsule endoscope is greater than 1 again for athird period of time following the second period of time after thecapsule endoscope is swallowed by a human subject.
 26. The capsuleendoscope of claim 1, wherein the pouch is configured such that thespecific gravity (SG) of the capsule endoscope is less than 1 for morethan 4 hours but less than 12 hours after the pouch is exposed to bodilyliquids by swallowing the capsule endoscope.
 27. A capsule endoscope,comprising: a sensor system comprising a light source, an image sensorfor capturing image frames of a scene illuminated by the light source; ahousing adapted for being swallowed, wherein the housing encloses thesensor system; and at least one pouch containing an effervescent, thepouch being attached to the housing and being semi-permeable or porousto body liquid so that the effervescent is able to generate gas uponcontact with the body liquid, wherein the effervescent comprisesanhydrous acid; wherein said at least the pouch is encapsulated within adissolvable shell, dome or coating, and wherein specific gravity (SG) ofthe capsule endoscope is greater than 1 when the pouch is encapsulatedwithin the dissolvable shell, dome or coating and wherein the SG of thecapsule endoscope corresponds to a specific gravity of all components ofthe capsule endoscope collectively together; and wherein said at leastthe pouch is configured to control inflation and deflation periods ofsaid at least the pouch such that the capsule endoscope has the SG ofthe capsule endoscope greater than 1 for a first period of time, andless than 1 for a second period of time following the first period oftime, and wherein said at least the pouch is configured to controlinflation and deflation periods of said at least the pouch by selectingparameters from a parameter group comprising a combination of pouchmembrane type and pouch wall thickness to affect a rate of diffusion ofbody liquid into the pouch.